Analysis of the chronic intake of and withdrawal from diazepam on emotional reactivity and sensory information processing in rats

Ross, Jas; Castilho, V.M.; Brandão, ML; Nobre, Manoel Jorge

doi:10.1016/j.pnpbp.2007.12.013

Cited by 8 publications

(3 citation statements)

References 69 publications

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“…Conversely, anxiolytic drugs increase social interaction, an effect not seen in the present study. Additionally, PPI does not seem to be modulate by acute, chronic or deprivation of treatment with benzodiazepines ( Rigdon and Viik, 1991 ; De Ross et al, 2008 ).…”

Section: Discussionmentioning

confidence: 98%

Cannabidiol Administered During Peri-Adolescence Prevents Behavioral Abnormalities in an Animal Model of Schizophrenia

et al. 2018

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Schizophrenia is considered a debilitating neurodevelopmental psychiatric disorder and its pharmacotherapy remains problematic without recent major advances. The development of interventions able to prevent the emergence of schizophrenia would therefore represent an enormous progress. Here, we investigated whether treatment with cannabidiol (CBD – a compound of Cannabis sativa that presents an antipsychotic profile in animals and humans) during peri-adolescence would prevent schizophrenia-like behavioral abnormalities in an animal model of schizophrenia: the spontaneously hypertensive rat (SHR) strain. Wistar rats and SHRs were treated with vehicle or CBD from 30 to 60 post-natal days. In experiment 1, schizophrenia-like behaviors (locomotor activity, social interaction, prepulse inhibition of startle and contextual fear conditioning) were assessed on post-natal day 90. Side effects commonly associated with antipsychotic treatment were also evaluated: body weight gain and catalepsy throughout the treatment, and oral dyskinesia 48 h after treatment interruption and on post-natal day 90. In experiment 2, serum levels of triglycerides and glycemia were assessed on post-natal day 61. In experiment 3, levels of BDNF, monoamines, and their metabolites were evaluated on post-natal days 61 and 90 in the prefrontal cortex and striatum. Treatment with CBD prevented the emergence of SHRs’ hyperlocomotor activity (a model for the positive symptoms of schizophrenia) and deficits in prepulse inhibition of startle and contextual fear conditioning (cognitive impairments). CBD did not induce any of the potential motor or metabolic side effects evaluated. Treatment with CBD increased the prefrontal cortex 5-HIAA/serotonin ratio and the levels of 5-HIAA on post-natal days 61 and 90, respectively. Our data provide pre-clinical evidence for a safe and beneficial effect of peripubertal and treatment with CBD on preventing positive and cognitive symptoms of schizophrenia, and suggest the involvement of the serotoninergic system on this effect.

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Section: Discussionmentioning

confidence: 98%

Cannabidiol Administered During Peri-Adolescence Prevents Behavioral Abnormalities in an Animal Model of Schizophrenia

et al. 2018

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“…Thereafter, the PPI modulation of the acoustic startle was tested in two different protocols. Protocol 1 (experiments 1, 3, 4 and 5): consisted of 60 trials pseudorandomly divided into four different categories presented with an inter-trial interval of 20 s: 20 presentations of pulse alone (120 dB, 50 ms duration), 10 presentations of prepulse alone (75 dB, 3000 Hz frequency, 20 ms duration), 20 presentations of prepulse + pulse (with 50 ms interval) and 10 no stimuli trials (stabilimeter recordings obtained when no stimulus was presented) (adapted from Ross et al, 2008). Protocol 2 (experiment 2): consisted of 74 trials pseudorandomly divided into seven different categories presented with an inter-trial interval of 20 s: 20 presentations of pulse alone (120 dB, 50 ms duration), 8 presentations of each prepulse intensity alone (70,75 and 80 dB, 3000 Hz frequency, 20 ms duration) and 10 presentations of each prepulse intensity + pulse (with 50 ms interval) (adapted from Gururajan et al, 2010).…”

Section: Methodsmentioning

confidence: 99%

Spontaneously Hypertensive Rats (SHR) present deficits in prepulse inhibition of startle specifically reverted by clozapine

Levin

Calzavara

Santos

et al. 2011

Progress in Neuro-Psychopharmacology and Biological Psychiatry

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Deficits in an operational measure of sensorimotor gating - the prepulse inhibition of startle (PPI) - are presented in psychiatric disorders such as schizophrenia, bipolar disorder, and attention deficit/hyperactivity disorder (ADHD). Some previous studies showed that the spontaneously hypertensive rats (SHR) present PPI deficit. Although SHR is suggested as an animal model to study ADHD, we have suggested that the behavioral phenotype of this strain mimics some aspects of schizophrenia. The aim of this study was to characterize the PPI response in SHR. Pharmacological characterization consisted in the evaluation of the effects of the following drugs administered to adult Wistar rats (WR) and SHR previously to the PPI test: amphetamine (used for ADHD and also a psychotomimetic drug), haloperidol and clozapine (antipsychotic drugs), metoclopramide (dopamine antagonist without antipsychotic properties) and carbamazepine (mood stabilizer). Our results showed that SHR presented reduced PPI. This deficit was similar to that induced by amphetamine in WR. Only the atypical antipsychotic clozapine improved the PPI deficit observed in SHR. These findings reinforce the SHR strain as an animal model to study several aspects of schizophrenia, including the abnormalities in sensorimotor gating associated with this disease.

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“…It is noteworthy that cocaine withdrawal was recently shown to lead to long-term changes in KOR-modulated limbic circuits [ 113 ], which suggests a ubiquitous role of opiate systems in mediating affective distress during withdrawal from multiple drugs of abuse. Separate lines of research have found that withdrawal from drugs of abuse that act on GABAergic transmission, such as ethanol, leads to increased rates of 22-kHz USVs relative to saline-treated control animals [ 92 , 115 - 117 ]. Moreover, administration of a KOR antagonist, nor-binaltorphimine (nor-BNI), attenuated the increase in 22-kHz USVs during acute ethanol withdrawal, which suggests involvement of KOR circuits in underlying this opposing process [ 93 ].…”

Section: Drug Withdrawal and Affective Distress: Evidence From Usvsmentioning

confidence: 99%

Ultrasonic Vocalizations as a Measure of Affect in Preclinical Models of Drug Abuse: A Review of Current Findings

Barker¹,

Simmons²,

West³

2015

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The present review describes ways in which ultrasonic vocalizations (USVs) have been used in studies of substance abuse. Accordingly, studies are reviewed which demonstrate roles for affective processing in response to the presentation of drug-related cues, experimenter- and self-administered drug, drug withdrawal, and during tests of relapse/reinstatement. The review focuses on data collected from studies using cocaine and amphetamine, where a large body of evidence has been collected. Data suggest that USVs capture animals’ initial positive reactions to psychostimulant administration and are capable of identifying individual differences in affective responding. Moreover, USVs have been used to demonstrate that positive affect becomes sensitized to psychostimulants over acute exposure before eventually exhibiting signs of tolerance. In the drug-dependent animal, a mixture of USVs suggesting positive and negative affect is observed, illustrating mixed responses to psychostimulants. This mixture is predominantly characterized by an initial bout of positive affect followed by an opponent negative emotional state, mirroring affective responses observed in human addicts. During drug withdrawal, USVs demonstrate the presence of negative affective withdrawal symptoms. Finally, it has been shown that drug-paired cues produce a learned, positive anticipatory response during training, and that presentation of drug-paired cues following abstinence produces both positive affect and reinstatement behavior. Thus, USVs are a useful tool for obtaining an objective measurement of affective states in animal models of substance abuse and can increase the information extracted from drug administration studies. USVs enable detection of subtle differences in a behavioral response that might otherwise be missed using traditional measures.

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Analysis of the chronic intake of and withdrawal from diazepam on emotional reactivity and sensory information processing in rats

Cited by 8 publications

References 69 publications

Cannabidiol Administered During Peri-Adolescence Prevents Behavioral Abnormalities in an Animal Model of Schizophrenia

Cannabidiol Administered During Peri-Adolescence Prevents Behavioral Abnormalities in an Animal Model of Schizophrenia

Spontaneously Hypertensive Rats (SHR) present deficits in prepulse inhibition of startle specifically reverted by clozapine

Ultrasonic Vocalizations as a Measure of Affect in Preclinical Models of Drug Abuse: A Review of Current Findings

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